Product Image

Contributor Information

  • Name Laurent Rigoreau
  • Institute Newcastle University

Tool Details

  • Tool name: Dual DNA-PK/PI3K inhibitor KU-0060648 Small Molecule (Tool Compound)
  • Molecular formula: C33H34N4O4S
  • Tool type: Small molecules
  • Tool sub-type: Inhibitor
  • Purpose: Inhibitor
  • Molecular weight of the target: 582.71
  • Application: KU-0060648 enhances the anti-tumour activity of etoposide in both MCF7 and SW620 xenograft models, and has single-agent activity in the MCF7 xenograft model. KU-0060648 exhibits differential effects on growth inhibition, but is not profoundly cytotoxic in a panel of human cancer cell lines. It inhibits DNA-PK and PI-3K with greater potency in MCF7 than SW620 cell using cell-based assays. Five-day exposure to 1 mM KU-0060648 inhibits cell proliferation by more than 95% in MCF7 cells but only by 55% in SW620 cells. In clonogenic survival assays, KU-0060648 increases the cytotoxicity of etoposide and doxorubicin across the panel of DNA-PKcs-proficient cells, but not in DNA-PKcs-deficient cells, confirming that enhanced cytotoxicity of the topoisomerase II poisons etoposide and doxorubicin is due to DNA-PK inhibition
  • Description: KU-0060648 is a dual PI3-K and DNA-PK inhibitor (IC50 values are <0.1, 0.5, 4 and 19 nM for PI 3-Kd, PI 3-K?, PI 3-Ka and DNA-PK respectively). It inhibits proliferation of MCF7 cells in vitro and delays growth of MCF7 xenografts in mice. KU-0060648 can also enhance CRISP-Cas9-mediated homology-directed repair (HDR) efficiency, and attenuate nonhomologous end-joining (NHEJ).
  • Research area: Cancer; Cell Cycle
  • IC50: inhibitor of DNA-PK and PI3KÎą, PI3Kβ, PI3Kδ with IC50 of 8.6 nM and 4 nM, 0.5 nM, 0.1 nM respectively, less inhibition of PI3KÎł with IC50 of 0.59 ÎźM.

  • For Research Use Only

Target Details

  • Target molecular weight: 582.71
  • Primary target: Dual PI 3-K and DNA-PK inhibitor

Application Details

  • Application: KU-0060648 enhances the anti-tumour activity of etoposide in both MCF7 and SW620 xenograft models, and has single-agent activity in the MCF7 xenograft model. KU-0060648 exhibits differential effects on growth inhibition, but is not profoundly cytotoxic in a panel of human cancer cell lines. It inhibits DNA-PK and PI-3K with greater potency in MCF7 than SW620 cell using cell-based assays. Five-day exposure to 1 mM KU-0060648 inhibits cell proliferation by more than 95% in MCF7 cells but only by 55% in SW620 cells. In clonogenic survival assays, KU-0060648 increases the cytotoxicity of etoposide and doxorubicin across the panel of DNA-PKcs-proficient cells, but not in DNA-PKcs-deficient cells, confirming that enhanced cytotoxicity of the topoisomerase II poisons etoposide and doxorubicin is due to DNA-PK inhibition

Handling

  • Purity: 582.71 g/mol
  • Solubility: Soluble to 100 mM in 2eq.HCl
  • Storage conditions: Store at -20°C
  • Shipping conditions: Dry Ice

Documentation

    Download Icon
    Download Icon
    Download Icon
    Download Icon
  • Available on request

Related Tools

Product Image

ABQ-38

#158327
Product Image

Isobenzofuran analog of sclerophytin A (8b) small molecule

#158014
Product Image

Glucose-6-phosphate Dehydrogenase inhibitor G6PD Small Molecule (Tool Compound)

#160405

References

  • •  Robert et al. 2015. Genome Med. 7(1):93. PMID: 26307031.
  • •  Pharmacological inhibition of DNA-PK stimulates Cas9-mediated genome editing.
  • •  Munck et al. 2012. Mol Cancer Ther. 11(8):1789-98. PMID: 22576130.
  • •  Chemosensitization of cancer cells by KU-0060648, a dual inhibitor of DNA-PK and PI-3K.